Virological Characterization of the First 2 COVID-19 Patients Diagnosed in Italy: Phylogenetic Analysis, Virus Shedding Profile From Different Body Sites, and Antibody Response Kinetics

Author:

Colavita Francesca1,Lapa Daniele1,Carletti Fabrizio1,Lalle Eleonora1,Messina Francesco1,Rueca Martina1,Matusali Giulia1,Meschi Silvia1,Bordi Licia1,Marsella Patrizia1,Nicastri Emanuele1,Marchioni Luisa1,Mariano Andrea1,Scorzolini Laura1,Ascoli Bartoli Tommaso1,Di Caro Antonino1ORCID,Ippolito Giuseppe1,Capobianchi Maria Rosaria1,Castilletti Concetta1,Abbate Isabella1,Agrati Chiara1,Aleo Loredana1,Alonzi Tonino1,Amendola Alessandra1,Apollonio Claudia1,Arduini Nicolina1,Bartolini Barbara1,Berno Giulia1,Biancone Silvia1,Biava Mirella1,Bibbò Angela1,Bordi Licia1,Brega Carla1,Canali Marco1,Cannas Angela1,Capobianchi Maria Rosaria1,Carletti Fabrizio1,Carrara Stefania1,Casetti Rita1,Castilletti Concetta1,Chiappini Roberta1,Ciafrone Lucia1,Cimini Eleonora1,Coen Sabrina1,Colavita Francesca1,Condello Rossella1,Coppola Antonio1,D’Arezzo Silvia1,Di Caro Antonino1,Di Filippo Stefania1,Di Giuli Chiara1,Fabeni Lavinia1,Felici Luisa1,Ferraioli Valeria1,Forbici Federica1,Garbuglia Anna Rosa1,Giombini Emanuela1,Gori Caterina1,Graziano Silvia1,Gruber Cesare Ernesto Maria1,Khouri Daniele1,Lalle Eleonora1,Lapa Daniele1,Leone Barbara1,Marsella Patrizia1,Massimino Chiara1,Matusali Giulia1,Mazzarelli Antonio1,Meschi Silvia1,Messina Francesco1,Minosse Claudia1,Montaldo Claudia1,Neri Stefania1,Nisii Carla1,Petrivelli Elisabetta1,Petroni Fabrizio1,Petruccioli Elisa1,Pisciotta Marina1,Pizzi Daniele1,Prota Gianluca1,Raparelli Fabrizio1,Rozera Gabriella1,Rueca Martina1,Sabatini Rossella1,Sarti Silvia1,Sberna Giuseppe1,Sciamanna Roberta1,Selleri Marina1,Selvaggi Carla1,Sias Catia1,Stellitano Chiara1,Toffoletti Antonietta1,Truffa Silvia1,Turchi Federica1,Valli Maria Beatrice1,Venditti Carolina1,Vescovo Tiziana1,Vincenti Donatella1,Vulcano Antonella1,Zambelli Emma1,Abbonizio Maria Alessandra1,Agrati Chiara1,Albarello Fabrizio1,Amadei Gioia1,Amendola Alessandra1,Antonini Mario1,Barbaro Raffaella1,Bartolini Barbara1,Benigni Martina1,Bevilacqua Nazario1,Bordi Licia1,Bordoni Veronica1,Branca Marta1,Campioni Paolo1,Capobianchi Maria Rosaria1,Caporale Cinzia1,Caravella Ilaria1,Carletti Fabrizio1,Castilletti Concetta1,Chiappini Roberta1,Ciaralli Carmine1,Colavita Francesca1,Corpolongo Angela1,Cristofaro Massimo1,Curiale Salvatore1,D’Abramo Alessandra1,Dantimi Cristina1,De Angelis Alessia1,De Angelis Giada1,Di Lorenzo Rachele1,Di Stefano Federica1,Ferraro Federica1,Fiorentini Lorena1,Frustaci Andrea1,Gallì Paola1,Garotto Gabriele1,Giancola Maria Letizia1,Giansante Filippo1,Giombini Emanuela1,Greci Maria Cristina1,Ippolito Giuseppe1,Lalle Eleonora1,Lanini Simone1,Lapa Daniele1,Lepore Luciana1,Lucia Andrea1,Lufrani Franco1,Macchione Manuela1,Marani Alessandra1,Marchioni Luisa1,Mariano Andrea1,Marini Maria Cristina1,Maritti Micaela1,Matusali Giulia1,Meschi Silvia1,Messina Francesco1,Montaldo Chiara1,Murachelli Silvia1,Nicastri Emanuele1,Noto Roberto1,Palazzolo Claudia1,Pallini Emanuele1,Passeri Virgilio1,Pelliccioni Federico1,Petrecchia Antonella1,Petrone Ada1,Petrosillo Nicola1,Pianura Elisa1,Pisciotta Maria1,Pittalis Silvia1,Proietti Costanza1,Puro Vincenzo1,Rinonapoli Gabriele1,Rueca Martina1,Sacchi Alessandra1,Sanasi Francesco1,Santagata Carmen1,Scarcia Silvana1,Schininà Vincenzo1,Scognamiglio Paola1,Scorzolini Laura1,Stazi Giulia1,Vaia Francesco1,Vairo Francesco1,Valli Maria Beatrice1,Abbate Isabella1,Agrati Chiara1,Aleo Loredana1,Alonzi Tonino1,Amendola Alessandra1,Apollonio Claudia1,Arduini Nicolina1,Bartolini Barbara1,Berno Giulia1,Biancone Silvia1,Biava Mirella1,Bibbò Angela1,Bordi Licia1,Brega Carla1,Canali Marco1,Cannas Angela1,Capobianchi Maria Rosaria1,Carletti Fabrizio1,Carrara Stefania1,Casetti Rita1,Castilletti Concetta1,Chiappini Roberta1,Ciafrone Lucia1,Cimini Eleonora1,Coen Sabrina1,Colavita Francesca1,Condello Rossella1,Coppola Antonio1,D’Arezzo Silvia1,Di Caro Antonino1,Di Filippo Stefania1,Di Giuli Chiara1,Fabeni Lavinia1,Felici Luisa1,Ferraioli Valeria1,Forbici Federica1,Garbuglia Anna Rosa1,Giombini Emanuela1,Gori Caterina1,Graziano Silvia1,Gruber Cesare Ernesto Maria1,Khouri Daniele1,Lalle Eleonora1,Lapa Daniele1,Leone Barbara1,Marsella Patrizia1,Massimino Chiara1,Matusali Giulia1,Mazzarelli Antonio1,Meschi Silvia1,Messina Francesco1,Minosse Claudia1,Montaldo Claudia1,Neri Stefania1,Nisii Carla1,Petrivelli Elisabetta1,Petroni Fabrizio1,Petruccioli Elisa1,Pisciotta Marina1,Pizzi Daniele1,Prota Gianluca1,Raparelli Fabrizio1,Rozera Gabriella1,Rueca Martina1,Sabatini Rossella1,Sarti Silvia1,Sberna Giuseppe1,Sciamanna Roberta1,Selleri Marina1,Selvaggi Carla1,Sias Catia1,Stellitano Chiara1,Toffoletti Antonietta1,Truffa Silvia1,Turchi Federica1,Valli Maria Beatrice1,Venditti Carolina1,Vescovo Tiziana1,Vincenti Donatella1,Vulcano Antonella1,Zambelli Emma1,Abbonizio Maria Alessandra1,Agrati Chiara1,Albarello Fabrizio1,Amadei Gioia1,Amendola Alessandra1,Antonini Mario1,Barbaro Raffaella1,Bartolini Barbara1,Benigni Martina1,Bevilacqua Nazario1,Bordi Licia1,Bordoni Veronica1,Branca Marta1,Campioni Paolo1,Capobianchi Maria Rosaria1,Caporale Cinzia1,Caravella Ilaria1,Carletti Fabrizio1,Castilletti Concetta1,Chiappini Roberta1,Ciaralli Carmine1,Colavita Francesca1,Corpolongo Angela1,Cristofaro Massimo1,Curiale Salvatore1,D’Abramo Alessandra1,Dantimi Cristina1,De Angelis Alessia1,De Angelis Giada1,Di Lorenzo Rachele1,Di Stefano Federica1,Ferraro Federica1,Fiorentini Lorena1,Frustaci Andrea1,Gallì Paola1,Garotto Gabriele1,Giancola Maria Letizia1,Giansante Filippo1,Giombini Emanuela1,Greci Maria Cristina1,Ippolito Giuseppe1,Lalle Eleonora1,Lanini Simone1,Lapa Daniele1,Lepore Luciana1,Lucia Andrea1,Lufrani Franco1,Macchione Manuela1,Marani Alessandra1,Marchioni Luisa1,Mariano Andrea1,Marini Maria Cristina1,Maritti Micaela1,Matusali Giulia1,Meschi Silvia1,Messina Francesco1,Montaldo Chiara1,Murachelli Silvia1,Nicastri Emanuele1,Noto Roberto1,Palazzolo Claudia1,Pallini Emanuele1,Passeri Virgilio1,Pelliccioni Federico1,Petrecchia Antonella1,Petrone Ada1,Petrosillo Nicola1,Pianura Elisa1,Pisciotta Maria1,Pittalis Silvia1,Proietti Costanza1,Puro Vincenzo1,Rinonapoli Gabriele1,Rueca Martina1,Sacchi Alessandra1,Sanasi Francesco1,Santagata Carmen1,Scarcia Silvana1,Schininà Vincenzo1,Scognamiglio Paola1,Scorzolini Laura1,Stazi Giulia1,Vaia Francesco1,Vairo Francesco1,Valli Maria Beatrice1,

Affiliation:

1. National Institute for Infectious Diseases “L. Spallanzani” IRCCS, Rome, Italy

Abstract

Abstract Background The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. We report the detection of viral RNA from different anatomical districts and the antibody profile in the first 2 COVID-19 cases diagnosed in Italy. Methods We tested for SARS-CoV-2 RNA clinical samples, either respiratory and nonrespiratory (ie, saliva, serum, urine, vomit, rectal, ocular, cutaneous, and cervico-vaginal swabs), longitudinally collected from both patients throughout the hospitalization. Serological analysis was carried out on serial serum samples to evaluate IgM, IgA, IgG, and neutralizing antibody levels. Results SARS-CoV-2 RNA was detected since the early phase of illness, lasting over 2 weeks in both upper and lower respiratory tract samples. Virus isolate was obtained from acute respiratory samples, while no infectious virus was rescued from late respiratory samples with low viral RNA load, collected when serum antibodies had been developed. Several other specimens came back positive, including saliva, vomit, rectal, cutaneous, cervico-vaginal, and ocular swabs. IgM, IgA, and IgG were detected within the first week of diagnosis, with IgG appearing earlier and at higher titers. Neutralizing antibodies developed during the second week, reaching high titers 32 days after diagnosis. Conclusions Our longitudinal analysis showed that SARS-CoV-2 RNA can be detected in different body samples, which may be associated with broad tropism and different spectra of clinical manifestations and modes of transmission. Profiling antibody response and neutralizing activity can assist in laboratory diagnosis and surveillance actions.

Funder

Ministry of Health

European Commission–Horizon 2020

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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